Редактирование: SDC1

Syndecan-1 precursor (SYND1) (CD138 antigen) [SDC]

==Publications==

{{medline-entry
|title=Olmesartan alleviates bleomycin-mediated vascular smooth muscle cell senescence via the miR-665/[[SDC1]] axis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33042414
|abstract=Olmesartan (OMST) is a new angiotensin II receptor antagonist recently approved by the FDA to treat cardiovascular diseases. We investigated the molecular mechanisms by which OMST regulates vascular senescence. In the present study, bleomycin ([[BLM]]) was used to induce senescence in vascular smooth muscle cells (VSMCs); after which, the cells were treated with OMST. The effects of OMST on [[BLM]]-mediated cell senescence were evaluated using cell adhesion, NAD /NADH, and Annevin V/PI double staining assays, as well as by immunofluorescence staining of γH2AX, Edu flow cytometry, and evaluations of senescence-associated β-gal activity. Differentially expressed microRNAs (DEMs) were identified by miRNA microarray assays, and subsequently validated by quantitative real time PCR. Bisulfite sequencing PCR (BSP) was used to detect the methylation status of the miR-665 promoter. The target genes of miR-665 were predicted and confirmed using luciferase reporter assays. We found that miR-665 was upregulated in VSMCs in response to [[BLM]]-induced cellular senescence. BSP studies revealed that CpG sites in the promoter region of the [i]miR-665[/i] gene underwent extensive demethylation during [[BLM]]-induced cellular senescence, and there was a concomitant up-regulation of miR-665 expression. [[SDC1]] mRNA was identified as a direct target of miR-665. Either miR-665 overexpression or [[SDC1]] knockdown significantly reversed the effects of OMST on [[BLM]]-induced VSMC senescence. Moreover, [[SDC1]] overexpression partially reversed the changes that occurred in cells with [[BLM]]-induced senescence caused by miR-665 overexpression. Our findings suggest that the miR-665/[[SDC1]] axis functions as a vital modulator of VSMC senescence, and may represent a novel biological target for treating atherosclerosis.

|keywords=* Atherosclerosis
* MiR-665
* SDC1
* olmesartan
* vascular smooth muscle cell senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540088
}}
{{medline-entry
|title=Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32530114
|abstract=Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 ([[PAPSS2]]) induces cellular senescence through augmented fibroblast growth factor receptor 1 ([[FGFR1]]) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented [[FGFR1]] signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 ([[SDC1]]) exhibited typical senescence phenotypes, and those depleted of [[PAPSS2]]-, [[SDC1]]-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased [[FGFR1]] internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated [[FGFR1]]- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated [[FGFR1]] endocytosis contributed to cellular senescence through the [[FGFR1]]-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented [[FGFR1]]-AKT-p53-p21 signaling, and decreased [[SDC1]] expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of [[SDC1]] expression and [[FGFR1]] internalization, and an increase in [[FGFR1]]-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated [[SDC1]] plays a critical role in preventing cellular senescence through the regulation of [[FGFR1]] endocytosis.

|keywords=* FGFR1
* SDC1
* cellular senescence
* endocytosis
* heparan sulfation
|full-text-url=https://sci-hub.do/10.1096/fj.201902714R
}}
{{medline-entry
|title=Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28973369
|abstract=To determine the impact of the loss of syndecan 1 ([[SDC1]]) on intraepithelial corneal nerves (ICNs) during homeostasis, aging, and in response to 1.5-mm trephine and debridement injury. Whole-mount corneas are used to quantify ICN density and thickness over time after birth and in response to injury in [[SDC1]]-null and wild-type (WT) mice. High-resolution three-dimensional imaging is used to visualize intraepithelial nerve terminals (INTs), axon fragments, and lysosomes in corneal epithelial cells using antibodies against growth associated protein 43 (GAP43), βIII tubulin, and [[LAMP1]]. Quantitative PCR was performed to quantify expression of [[SDC1]], [[SDC2]], [[SDC3]], and [[SDC4]] in corneal epithelial mRNA. Phagocytosis was assessed by quantifying internalization of fluorescently labeled 1-μm latex beads. Intraepithelial corneal nerves innervate the corneas of [[SDC1]]-null mice more slowly. At 8 weeks, ICN density is less but thickness is greater. Apically projecting intraepithelial nerve terminals and lysosome-associated membrane glycoprotein 1 ([[LAMP1]]) are also reduced in unwounded [[SDC1]]-null corneas. Quantitative PCR and immunofluorescence studies show that [[SDC3]] expression and localization are increased in [[SDC1]]-null ICNs. Wild-type and [[SDC1]]-null corneas lose ICN density and thickness as they age. Recovery of axon density and thickness after trephine but not debridement wounds is slower in [[SDC1]]-null corneas compared with WT. Experiments assessing phagocytosis show reduced bead internalization by [[SDC1]]-null epithelial cells. Syndecan-1 deficiency alters ICN morphology and homeostasis during aging, reduces epithelial phagocytosis, and impairs reinnervation after trephine but not debridement injury. These data provide insight into the mechanisms used by sensory nerves to reinnervate after injury.
|mesh-terms=* Aging
* Animals
* Axons
* Cornea
* Corneal Injuries
* Disease Models, Animal
* Epithelium, Corneal
* Homeostasis
* Mice
* Mice, Inbred BALB C
* Nerve Fibers
* Syndecan-1
* Syndecans

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627677
}}
{{medline-entry
|title=Ionizing radiation-mediated premature senescence and paracrine interactions with cancer cells enhance the expression of syndecan 1 in human breast stromal fibroblasts: the role of TGF-β.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27434331
|abstract=The cell surface proteoglycan syndecan 1 ([[SDC1]]) is overexpressed in the malignant breast stromal fibroblasts, creating a favorable milieu for tumor cell growth. In the present study, we found that ionizing radiation, a well-established treatment in human breast cancer, provokes premature senescence of human breast stromal fibroblasts in vitro, as well as in the breast tissue in vivo. These senescent cells were found to overexpress [[SDC1]] both in vitro and in vivo. By using a series of specific inhibitors and siRNA approaches, we showed that this [[SDC1]] overexpression in senescent cells is the result of an autocrine action of Transforming Growth Factor-β (TGF-β) through the Smad pathway and the transcription factor Sp1, while the classical senescence pathways of p53 or p38 MAPK - NF-kB are not involved. In addition, the highly invasive human breast cancer cells MDA-[[MB]]-231 (in contrast to the low-invasive MCF-7) can also enhance [[SDC1]] expression, both in early-passage and senescent fibroblasts via a paracrine action of TGF-β. The above suggest that radiation-mediated premature senescence and invasive tumor cells, alone or in combination, enhance [[SDC1]] expression in breast stromal fibroblasts, a poor prognostic factor for cancer growth, and that TGF-β plays a crucial role in this process.
|mesh-terms=* Breast Neoplasms
* Cell Line, Tumor
* Cellular Senescence
* Female
* Fibroblasts
* Humans
* Mammary Glands, Human
* NF-kappa B
* Paracrine Communication
* Radiation, Ionizing
* Signal Transduction
* Smad Proteins
* Syndecan-1
* Transforming Growth Factor beta
|keywords=* TGF-β
* breast stroma
* cancer
* ionizing radiation
* senescence
* syndecan 1
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032688
}}